3-substituted 7-carbalkoxyamino-coumarins



coumarin.

nited State S-SUBSTITUTED 7-CARBALKOXYAMINO- COUMARENS HenrichHau'serrnann, Basel, Switzerland, assignor to 5. R. Geigy, A.G., Basel,Switzerland, :1 Swiss firm No Drawing. Original application October 31,1955, erial No. 544,045, now Patent No. 2,88L185, dated April 7, 1959.Divided and this application August 25, 1958, Serial No. 757,135

Claims priority, application witzeriand November 12, 1954 Claims. (Cl.260-43432) marin derivatives as well as, as industrial product, the

material brightened with the aid of these compounds.

7-aminocoumarin compounds have already been suggested more than once asoptical brightening agents for the most different types of substratasuch as soap, cellulose fibers, wool, synthetic polypeptide fibers.However, 7-aminocoumarin compounds which are substituted in the3-position of the coumarin ring by a phenyl radical have not been knownup to now. The present invention is concerned with the production ofsuch new 3-substituted 7-aminocoumarin compounds and derivativesthereof.

It has been found that new valuable 3-substituted 7-acylaminocoumarinsare obtained if a benzaldehyde which contains in the 2-position ahydroxyl group or a substituent which can be converted into a hydroxylgroup and in the 4-position contains a substituted amino group or asubstituent which can be converted into an amino group, is condensed bymethods known per se with a derivative of acetic acid which contains aphenyl radical at the u-carbon atom, to form the correspondingS-phenylacrylic acid derivative. If desirable, then the group in theo-position to the acrylic group in the ,B-phenyl radical is liberated asa hydroxyl group and this, with the carboxyl function of the acrylicacid radi-- ,cal, closes the coumarin ring.

stituent producing the amino group in the 7-position is If necessary,the submodified to form this group which is further transformed into acarbalkoxyamino group at any stage desired during the reaction.

Benzaldehydes which can be used according to the invention are, forexample, the known 2-hydroxy-4- nitrobenzaldehyde and the2-hydroxy-4-acylaminobenzaldehydes obtainable therefrom by acylatingreduction. Particularly favorable, however, are theZ-alkoxy-benzaldehydes which contain ainitro, or preferably an acylaminogroup, in the -4-position which can be converted into the amino group.Because of disturbing side reactions, a primary amino group in the4-position is to be 7 avoided at all costs.

Examples of acetic acid derivatives which can be con- .densed and whichcontain phenyl substituents at the 2,929,822 ?a.tented Mar. 22, 1960compound is performed by methods known per se, for

boxylic acid ester, carboxylic acid amide, and the nitrile example inalcohol in the presence of caustic alkalies, of alkali alcoholates or ofpiperidine. If o-alkoxy aldehydes are used for the condensation, thenthe liberation of the hydroxyl group follows; it is performedadvantageously with anhydrous aluminum chloride in inert organicsolvents such as benzene, chlorobenzene or nitrobenzene, or in thealuminum chloride-sodium chloride melt, in the pyridine chlorohydratemelt or also with a solution of hydrogen bromide in glacial acetic acid.Often the coumarin ring is closed at the same time. For this, it is notnecessary that the carboxyl gorup of the acrylic acid radical should bein the free form; it can be in the modified form of the carboxylic acidester, carboxylic acid amide and, preferably, of the nitrile group.

if the coumarin ring has not been closed on the dealkylation of thealkoxy group or if a B-(Z-hydroxyphenyl)-acrylic acid derivative isobtained as reaction above.

Those 3-phenyl-7-acylamino-coumarins have proved to be particularlyvaluable optical brightening agents, in which the acyl radical is acarbonic acid half ester, in particular, a carbalkoxy group derived froma lower alkanol with up to 4 carbon atoms which may include ethergroups. The acid radical can already be present in the starting materialor it can be introduced into the 3-phenyl-7-aminocoumarin only in thelast'step of the reaction. In the latter case, a3-phenyl-7-aminocoumarin is advantageously reacted in organic solution,and if desired in the presence of acid binding agents and of tertiarynitrogen bases favoring the acylation, with chloroformic acid esters. Animportant modification of the process according to the present inventionconsists in converting the 3-phenyl-7-aminocoumarins by methods knownper se with phosgene in inert organic solvents while warming, into the3-phenylcoumarinyl-7- isocyanates and reacting these with alcohols toform urethanes.

Thus, the new 3-phenyl 7-carbalkoxyaminocoumarin compounds correspond tothe general Formula I BE R2 Rio-o O-NH- wherein R represents a loweraliphatic radical comprisyellowish powder.

cence in the acylated condition. They can be used for example for theoptical brightening of polyamide and polyurethane fibers, and ofcellulose acetate. They can also be incorporated in polymeric syntheticsubstances such as polyvinyl chloride, polystyrol or polyethylene andthese polymers can be worked up to form fluorescent plastic foils.

This application is divided out of my copending application Serial No.544,045, filed October-31, 1955 (now Example 1.--Preparatiort of3-phenyl-7-aminacoumarin (a) 19.3 parts of2-methoXy-4-acetylamino-benzaldehyde (J. Chem. Soc. 1741 (1927)) and11.7 parts of benzylcyanide are dissolved in 200 parts of 95% alcoholand the temperature is reduced to 25 -30. A solution of 7.5 parts of 50%caustic potash solution in 40 parts of 95% alcohol is quickly poured inwhile stirring. The temperature rises slightly and'after a few minutes afirm yellow precipitate is formed. The mixture is heated for 30 minutesat-40-45" to complete the reaction. After cooling to 20, theprecipitated yellow colored reaction product is filtered off, washedwith alcohol and water and dried. In this way 26 parts ofzx-Phenyl-ti-(Z-methoxy4 -acetylaminophenyl)-acrylonitrile are obtainedas a The product can be purified by recrystallization from times theamount of chlorobenzene, but this purification is not necessary for thefollowingreactionto close the ring. The recrystallized preparation meltsat 195 and has a yellow fluorescence in ultra-violet light.

(b) 63 parts of thea-phenyl-fi-'(2-methoxy-4-acetylaminophenyl)-acrylonitrile obtained aredistributed while stirring in 500 parts of abs. benzene and 160 parts ofpulverized anhydrous aluminum chloride are added. The temperature risesfrom to about 40. The yellowbrown reaction mixture is then boiled underreflux for 6 hours while stirring and, after cooling, 800 parts of iceand 100 parts of 30% hydrochloric acid are added. After the benzene hasbeen removed by steam distillation, the yellow precipitate obtained isfiltered of? under suction and'washed with water. The substance obtainedis not uniform and contains, apart from some 3-phenyl-7- aminocoumarin,the acetylation product thereof and in addition a non-cyclised product,from the analysis values and chemical properties of which it can bededuced that it is an acetylamino-hydroxy-carboxylic acid amide of theformula:

I OH CONHz This yellow mixture of substances is then boiled under refluxin a mixture of 700 parts of 85% acetic acid and 118 partsof 36%hydrochloric acid while stirring. The

parts of water whereupon complete hydrolysis into the free base andhydrochloric acid occurs. The yellow colored 3-phenyl-7-aminocoumarin soobtained which fluoresces an extraordinarily blue to blue-green color inalcoholic solution is filtered ofi, washed until the reac- Therelationship of parts by 4 tion is neutral and, after drying, it isrecrystallized from alcohol or chlorobenzene. In this way, 42-45 parts,i.e. 83-89% of the theoretical amount, of pure 3-phenyl-7- aminocoumarinare obtained, M.P. 208-209. The aminocoumarin crystallizes into yellowneedles and in organic solvents has a very intensive fluorescence whichcan vary according to the type of solvent from blue-violet (benzine) togreenish-blue (alcohol).

(c) 6 parts of u-phenyl-fl-(2-methoxy-4-acetylaminophenyl)-acrylonitrileobtained according to paragraph (a) above, are heated for 30 minuteswith 30 parts of pyridine chlorohydrate at ISO-200 and then the meltobtained is poured into 150 parts of water. The yellowbrown body whichprecipitates is filtered off, washed with water, dissolved hot in partsof pyridine, filtered and 10 parts of acetic anhydride are added. Oncooling, brownish colored crystals precipitate which are drawn off undersuction and purified by recrystallization from methylcellosolve.3-phenyl-7-acetylaminocoumarin is obtained in this way as almostcolorless needles which melt at 265. The acetyl derivative is convertedinto the 3-phenyl-7-aminocoumarin as described in the precedingparagraph (b) by boiling with concentrated hydrochloric acid.

(d) 4 parts of e-phenyl-fl-(2 methoxy-4-acetylaminophenyD-acrylonitrileobtained according to paragraph (a), are added to a melt of 32 parts ofaluminum chloride and 8 parts of sodium chloride. at l20l30 and thewhole is stirred at the. same temperature for 5 minutes. Ice and 30%hydrochloric acid are then added to the yellow melt, the yellow bodywhich precipitates is filtered off, washed and finally boiled withacetic acid-l-hydrochloric acid in a manner analogous to that describedin paragraph (b). Working up analogous to paragraph (1)) produces thesame 3-phenyl-7-aminocoumarin which melts at 208".

15.2 parts of p-chlorobenzyl cyanide and 19.3 parts of4-acetylamino-2-methoxybenzaldehyde in 200 parts of 95% alcohol arecondensed in a manner analogous to that described in (Example 1a) with7.5 parts of caustic potash solution. The a-(p-chlorophenyl)-fl-(2-methoxy 4 acetylaminophenyD acrylonitrile obtained crystallizes fromchlorobenzene in fine yellow clusters of needles, which melt at 250uncorrected. In ultra-violet light the substance fiuoresces brightgreenish yellow. In

order to convert the acrylonitrile derivative obtained into filtered andwashed until the reaction is neutral.

3-(p-chlorophenyl)-7-amihocoumarin,.it is added at 110- 115 to a melt of200 parts of anhydrous aluminum chloride, 40' parts of sodium chlorideand 10 parts of potassium cloride while stirring, and stirring iscontinued for 30 minutes at 105-110 until a homogeneous brown melt isobtained. The melt is then poured while stirring into amixture of 1000parts of ice and 100 parts of 30% hydrochloric acid and the whole is"heated for 1 hour at -90 while stirring. The yellow suspension obtainedis cooled to 20, the yellow precipitate is filtered ofi,

washed with water and then stirred for 3 hours at in a mixture of 300parts of 80% acetic acid and 50 parts of 30%hydro'chloric acid. The paleyellow precipitate obtained is filtered after being cooled, washed with80% acetic acid, stirred in 300 parts of water, again After drying, 21'parts of the crude 3-(p-chlorophenyl)-7-aminocoumarin are obtained as agreenish-yellow powder. The new compound crystallizes from chlorobenzenein small yellow crystalswliich'melt at 252 uncorrected.3-(pchlorophenyl)-7-arninocoumarin' fluoresces blue-green to"greenish'blue in alcohol and bright'pure blue in benzene or acetone.

The same productis obtained if in this example the 19.3 parts df2-methoxy=4 acetylaminobenzaldehyde are replaced by 20.7 parts of2-ethoxy-4-acetylamino'benzaldehyde (M.P. 136).

Example 3.Preparation of 3-(4'-methylphenyl)-7- 'ami-nocoumarin Example4.Preparation of 3-phenyl-coumarinyl-(7)- isocyanates O=Q=NOCH= G andothers I O O 23.7 parts of 3-phenyl-7-aminocoumarin are dissolved in1000 parts of abs. chlorobenzene at 110 and convened into thechlorohydrate by the introduction of abs. hydrogen chloride. The almostcolorless suspension of the base hydrochloride so obtained is thencooled to 50 and is reacted at a rising temperature while stirring withexcess phosgene. As soon as the temperature has reached 100- 110",phosgene is still introduced until the HCl formation is complete. Thetemperature is then raised to 130, upon which an almost completesolution is obtained. After hot filtration from the chlorobenzenesolution, the resulting 3-phenylcoumarinyl-(7)-isocyanate crystallizesout in colorless glittering little flakes. After cooling completely, thecrystals are drawn oil under suction, washed with some benzene and driedfor a short time. The yield is 22-24 parts, i.e. 83-92% of thetheoretical. The new isocyanate melts at 233 uncorrected, and in inertorganic solvents it has a fairly strong blue to violet fluorescence indaylight.

Because of its N=C=O group which can be easily hydrolyzed, theisocyanate itself is not so suitable as a brightening agent but it is avery valuable intermediate product for the production of numerous ureasand urethanes which are suitable as brightening agents.

'If in this example the 23.7 parts of 3-phenyl-7-aminocoumarin arereplaced by 25.1 parts of B-(p-methylphenyl)-7-aminocoumarin or by 27.15parts of 3-(p-chlorophenyl)-7-aminocoumarin, then the3-(p-methylphenyl)- coumarinyl-(7)-isocyanate (M.P. 214) or the3-(p-chlorophenyl)-coumarinyl-(7)-isocyanate (M.P. 225) respectively areobtained. These isocyanates are valuable intermediate products for theproduction of optical brightening agents.

4.74 parts of 3-phenyl-7-aminocoumarin are suspended in 250 parts byvolume of acetone, 10 parts of pulverized anhydrous potassium acetateare added and the whole is added over 1 hour at 55-65 while stirring to10 parts -.-.o'f chloroformic-acid ethyl ester.- After stirring for 1hour at 55-65 the reaction mixture is cooled to 0l0, the yellowishwhite. precipitate is filtered olf and washed free ofsalt with ,water.The 3-phenyl-7-carbethoxyaminocoumarin obtained crystallizes fromalcohol in pale yellow crystals which melt at 216-2l7. In alcohol theurethane fluoresces blue-violet and is suitable for the opticalbleaching of acetate silk and nylon. The same product is obtained if3-phenyl-coumarinyl-(7 -isocyanate is boiled for some hours under refluxin excess abs. ethanol. Analogous compounds (containing the3-(pmethylphenyl)- and 3-(p-chlorophenyl)- groups), useful asbrightening agents, are obtained if the isocyanates described in thelast paragraph of the preceding Example 4 are boiled with excessabsolute lower alkanols. The following urethanes which have similarproperties can be produced in an analogous manner:

CBhOCONH-Ph-Oou M.P. 237 uncorrected cmonromoooNrr-i-hcHdIIIZIIIIIIIIIII M P 209 CH:

CHOCONH-Ph- Cou M.P. 229

CH3(CHg) GH20CONH-PhCou M1. ornoomomooorrn-Pn-oou M.P.191

(-Ph-Cou means the 31 heuyl-coumarlnyl-(7) radical).

Example 6.--0ptical brightening of synthetic polypeptide fibers 10 partsof slightly yellowish nylon material are dyed for 30 minutes at 60-70 ina dyebath (liquor ratio 1:40) which contains 0.005 part of thebrightening agent obtained according to Example 5. The goods are rinsedwith cold water and dried in the air. The material so treated has a muchwhiter appearance than untreated material.

A very similar action is obtained if instead of the brightening agentaccording to Example 5, one according to the table of Example 5 is used.

Example 7.Optical brightening of cellulose acetate wherein R representsa member selected from the group consisting of lower alkyl and(lower)alkoxy(lower)alkyl and R represents a member selected from thegroup consisting of phenyl, methylphenyl and chlorophenyl radicals.

2. The 7-carbalkoxyamino-3-phenyl-coumarin of the formula:

3. The 7-carbalkoxyamino-3-phenyl-coumarin of the formula:

CHaO-C O-NH-

1. A 7-CARBALKOXYAMINOCOUMARIN DERATIVE HAVING THE GENERAL FORMULA: